Display Settings:


Send to:

Choose Destination
Gastroenterology. 2011 Jul;141(1):348-57, 357.e1-3. doi: 10.1053/j.gastro.2011.04.002. Epub 2011 Apr 12.

Inflammation promotes the loss of adeno-associated virus-mediated transgene expression in mouse liver.

Author information

  • 1Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-3403, USA.



Non-self transgenes delivered to mouse liver via adeno-associated virus (AAV) are expressed stably due to the induction of immune tolerance. However, such transgene expression has been reported to be lost in higher-order primates. We investigated whether inflammatory processes, which likely differ between species, impact the stability of transgene expression.


We developed a mouse model that mimics a scenario in which a subject that has received hepatic AAV-mediated gene transfer develops subsequent, vector-unrelated, systemic inflammation.


Inflammation eliminated previously stable expression of transgenes delivered by AAV; the limited tissue destruction and persistence of AAV genomes implicated pathways besides the cytotoxic T-cell response. Tumor necrosis factor-a down-regulated expression of the transgene from the AAV, indicating a role for similar inflammatory cytokines in such loss of transgene expression.


Inflammation can block AAV-mediated expression of transgenes in mouse liver. The presence of inflammation might therefore affect hepatic expression of transgenes from viral vectors in humans.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk